Prostate Cancer Trials: Salvage/Adjuvant and Oligometastatic Disease

Board Review Presentation
Radiation Oncology

Presentation Overview

  • Part 1: Salvage/Adjuvant Trials
    • Classical adjuvant vs observation trials
    • Modern adjuvant vs early salvage trials
    • Salvage + ADT trials
  • Part 2: Oligometastatic Prostate Cancer
    • Treatment of primary in M1 disease
    • SBRT to oligometastases
    • Systemic therapy intensification

Classical Adjuvant vs Observation RT Studies

  SWOG/RTOG 9019 (~2006) EORTC 22911 (~2005) ARO 96-02 (~2009)
Patients • Post-RP
• pT3 (SVI/ECE) or + margins
• Any PSA level allowed
~1/3 had PSA >0.2, & 5-10% had PSA >1		 • Post-RP
• pT2-T3N0 with either +margin, ECE, or SVI
• PSA ≤ 0.4		 • Post-RP
• pT3 (SVI/ECE) or + margin
• Undetectable PSA (randomized prior to post-op PSA)
Arms →adjuvant 60-64 Gy RT to prostate bed
→wait and see [salvage RT in 33%, med PSA 1.0]
No concurrent ADT		 →adjuvant 50 Gy to prostate bed +10 Gy boost
→wait and see [delayed salvage RT 70Gy in 55%, at med PSA 1.7]		 →adjuvant 60 Gy to prostate bed [PSA <0.1 required]
→wait and see RT strongly recommended at PSA rise
Results 10-yr BPFS 58% vs. 28%
OS and DMFS change seen at 15 years
10-yr OS 66% vs. 74%
15-yr OS 37% vs. 47%
15-yr DMFS 38% vs. 46%
10-yr toxicity: rectal complications 3% vs. 0%
urethral strictures 18% vs. 9%
urinary incontinence 6% vs. 3%		 10-yr BPFS 61% vs. 39% p<0.0001
10-yr LRR 7% vs. 16% p<0.0001
No change in DM, OS, or CSS at 10 years
10-yr toxicity:
No grade 4
Grade 3 increased 5.3% vs. 2.5%
Grade ≥2 GU increased 21% vs. 14%
Grade ≥2 GI similar 2.5% vs. 1.9%		 5-yr BPFS 72% RT vs. 54% P=0.0015
10-yr BPFS 56% vs. 35%
No change in OS or DM
Unknown how many received delayed salvage
10-yr toxicity: only one grade 3 late toxicity of GI. There were 3 grade 2 GU and 2 grade 2 GI.

Modern Adjuvant vs Early Salvage RT Studies

TROG-RAVES (2020) GETUG-AFU 17 (2020) RADICALS-RT
Patients • pT3a/b (SVI/ECE), or positive margin
• PSA ≤0.10
N = 333		 • Positive margins required in all
• pT3a/b, or pT4a
• PSA ≤0.10
N = 424		 • ≥1 of pT3a/b, T4, GS 7-10, pre-op PSA ≥10, or positive margins
• PSA ≤0.2
N = 1396
Arms →adjuvant RT 64 Gy /32fx
→salvage RT 64 Gy at PSA ≥0.2

>NO ADT or WPRT allowed		 Superiority
→adjuvant RT 66 Gy /33fx
→salvage RT 66 Gy at ≥0.2 and rising
(WPRT of 46 Gy optional)
> ADT required in all for 6 mos		 →adjuvant RT
→salvage RT at PSA failure
(PSA >0.1 & rising, or any PSA rising x3)
RT: 66Gy/33fx (2/3rd) | 52.5Gy/20fx (1/3rd)
(WPRT 56 Gy optional)
>ADT none vs. 6 mos vs. 24 mos (not random)
Results Salvage RT triggered in 50%

5-yr BPFS 86% vs. 87% (not noninferior)
8-yr BPFS 80% vs. 75%

grade ≥2 GU toxicity 70% vs. 54%
grade ≥2 GI toxicity 14% vs. 10%
Trial terminated early due to low events		 Salvage RT triggered in 54%

5-yr EFS 90-92%, not different

late grade ≥2 GU toxicity 27% vs. 7%
late grade ≥2 GI toxicity 8% vs. 5%
late ED grade ≥2 28% vs. 8%
Trial terminated early due to low events		 8-yr BPFS not different between adjuvant and salvage RT

GU incontinence 5.3% vs. 2.7% (p=0.008)

urethral stricture 8% vs. 5% (p=0.03)

See ARTISTIC

ARTISTIC Meta-analysis

  • Design: Meta-analysis of RAVES, RADICALS-RT, and GETUG-AFU 17
  • Patients: Combined data from 2,153 patients across three trials
  • Results:
    • 5-year event-free survival: 89% vs 88% (HR 0.95, 95% CI: 0.75-1.21)
    • No difference in biochemical progression-free survival
    • Lower rate of urinary toxicity with early salvage approach
    • Approximately 50% of patients in salvage arms avoided radiation entirely
  • Conclusion: Early salvage RT was non-inferior to adjuvant RT with lower toxicity
  • Key Message: Early salvage approach spares ~50% of patients from RT without compromising oncologic outcomes

Salvage + ADT Studies

RTOG 9601 GETUG-AFU 16 SPPORT RADICALS-HD
Patients • pT3N0 | T2N0 with positive margins
• PSA 0.2-4.0 after RP
• N = 760		 • pT2-T4a (bladder neck only)
• PSA 0.2-2.0
• N = 743		 • PSA ≥0.1 - 2.0
• T2-3N0/Nx, ±margin, GS ≤9
• Excluded pN1
• N = 1792		 • ≥1 of: pT3a/b, T4, GS 7-10, PSA ≥10, or +margins
• PSA ≤0.2
• 63% +margin, 70% ECE, 19% SVI
• N = 1480 (0v6m), 1523 (6v24m)
Arms →RT 64.8 Gy
→RT + 24 mo bicalutamide 		→RT 66 Gy alone
→RT + 6 mo ADT
46 Gy WPRT if Partin ≥10%		 →PB RT 64.8-70.2 Gy
→PB RT + 4-6 mo ADT
→WPRT + PB RT + 4-6 mo ADT 		Two 2-way comparisons:
→RT vs RT + 6m ADT
→RT + 6m vs RT + 24m ADT
RT: 66 Gy/33 fx or 52.5 Gy/20 fx
Overall Survival IMPROVED (p=0.04):
12-yr: 76% vs 71%
HR 0.77 (0.59-0.99)
Benefit if PSA >0.7
No benefit if PSA ≤0.6 		IMPROVED (p=0.036):
10-yr: 76% vs 86%
HR 0.69 (0.47-1.01) 		NOT DIFFERENT:
5-yr: 94-96%
(immature data) 		NO BENEFIT:
No OS improvement with any ADT
0v6m: HR 0.88 (0.65-1.19)
6v24m: HR 0.88 (0.66-1.17)
Metastasis-Free Survival IMPROVED:
12-yr: 76.3% vs 71.3%
HR 0.73 (0.61-0.87) 		IMPROVED (p=0.034):
10-yr: 69% vs 75%
HR 0.73 (0.54-0.98) 		Data not reported 0v6m: NO BENEFIT
HR 0.89 (0.69-1.14)
6v24m: IMPROVED (p=0.029)
10-yr: 72% vs 78%
HR 0.77 (0.61-0.97)
Progression-Free Survival IMPROVED:
10-yr FFP: 46% vs 30%
12-yr DM: 14.5% vs 23.0%
12-yr PC death: 6% vs 13% 		IMPROVED (p<0.0001):
10-yr: 49% vs 64%
HR 0.54 (0.43-0.68)
10-yr DM: 31% vs 25% 		IMPROVED (p<0.0001):
5-yr FFP: 71% vs 81% vs 87%
5-yr DM: 9% vs 6% vs 5%
5-yr castrate resistance: 3% vs 2% vs 1% 		10-yr BPFS ~75% (no difference)
10-yr DM: 7% vs 10% (adj vs salv, NS)
No difference by PSA level, GS, margins, or RT schedule
Key Points • Decipher can help if PSA 0.5-0.7
• Grade 3-4 GI similar: 7%
• Grade 3-4 GU: 2.7% vs 1.6% 		• Grade 3 GU: 8% vs 7%
• No toxicity difference 		• WPRT improved outcomes
• 5-yr regional failure: 5% vs 2% vs 1%
• Late G2+ toxicity similar 		• Largest salvage ADT trial
• Early salvage preferred (adj vs salv)
• Stricture: 13% vs 6% (adj vs salv)

KEY MESSAGE: 24m ADT improves outcomes for PSA >0.7 (RTOG 9601). RADICALS-HD shows 24m > 6m ADT for MFS, but 6m = none. No subgroup differences found.

Radicals HD

Salvage + ADT Studies

RTOG 9601 GETUG-AFU 16 SPPORT
Patients • pT3N0 | T2N0 with positive margins
• elevated PSA 0.2-4.0 after RP
• N = 760		 • pT2-T4a (bladder neck only)
• rising PSA of 0.2-2.0
• N = 743		 • PSA ≥0.1 - 2.0
• T2-3N0/Nx, with or without positive margin, Gleason ≤9, excluded pN1
• N = 1792
Arms →RT 64.8 Gy to prostate fossa
→RT with 24 months bicalutamide concurrently and adjuvant 		→66 Gy RT alone
→RT with 6 mos ADT
46 Gy WPRT given if Partin score ≥10% before RP and no LND		 →prostate bed (PB) RT 64.8-70.2 Gy
→PB RT + 4-6 mos ADT
→WPRT 45 Gy + PB RT + 4-6 mos ADT
Results 10-yr FFP: improved 46% vs. 30%
12-yr OS improved 76% vs. 71%
12-yr DM 14.5% vs. 23.0%
12-yr PC death 6% vs. 13%

No OS or DM benefit in PSA ≤0.6
OS benefit in PSA <0.7 with high Decipher score
Late grade 3-4 GI toxicity similar at 7%
Late grade 3-4 GU toxicity similar, 2.7 vs 1.6%		 ADT reduced DM, but did not improve OS
5, 10-yr PFS 62%/49% vs. 80%/64% ADT
10-yr DM 31% vs. 25% ADT

No change in OS

Grade 3 GU 8% vs. 7% (no toxicity difference apparently)		 5-yr FFP 71% vs. 81% vs. 87%
5-yr DM 9% vs. 6% vs. 5%
5-yr OS 94-96%, not different
5-yr BF (Phoenix) 20% vs. 14% vs. 8%
5-yr BF (≥0.4) 31% vs. 21% vs. 13%
5-yr castrate resistance 3% vs. 2% vs. 1%
5-yr regional failure 5% vs. 2% vs. 1%

Late grade 2+ toxicity (>3 mos) not different, except for worse 1-yr toxicity
DADSPORT

DADSPORT Meta-analysis

Duration of Androgen Suppression with Post-operative Radiotherapy
Meta-analysis of RTOG 9601, GETUG-AFU 16, NRG/RTOG 0534 (SPPORT), and RADICALS-HD

Included Trials: 4 trials • 4,452 men • 701 deaths • Median follow-up: 8 years • 100% of randomized patients

Treatment Comparison No. of Trials Events/Men HR (95% CI), p-value Significance
Overall Survival
HT (any duration) vs no HT 4 701/4452 0.89 (0.77-1.03), p=0.13 NS
6m HT vs no HT 3 419/3364 0.90 (0.74-1.09), p=0.28 NS
24m HT vs no HT 2 282/1088 0.89 (0.72-1.10), p=0.29 NS
Sensitivity analysis (excl. PSA >1.5) 4 650/4334 0.93 (0.80-1.08), p=0.35 NS
Metastasis-Free Survival
6m HT vs no HT 3 653/3364 0.82 (0.70-0.96), p=0.013 IMPROVED

Overall Survival

No clear improvement with HT
Similar effects for 6m and 24m duration
Results consistent in sensitivity analysis

Metastasis-Free Survival

6m HT significantly improves MFS
HR 0.82 (18% relative reduction)
24m HT data pending from 2 trials

KEY MESSAGE: 6 months of ADT improves MFS but not OS in salvage RT setting (aggregate data meta-analysis)

Included Trials: 4 trials • 4,452 men • 701 deaths • Median follow-up: 8 years • 100% of randomized patients
Important: Most trials excluded pN1 patients (SPPORT excluded pN1; RTOG 9601 was pN0/pNx only)

Treatment Comparison No. of Trials Events/Men HR (95% CI), p-value Significance
Overall Survival
HT (any duration) vs no HT 4 701/4452 0.89 (0.77-1.03), p=0.13 NS
6m HT vs no HT 3 419/3364 0.90 (0.74-1.09), p=0.28 NS
24m HT vs no HT 2 282/1088 0.89 (0.72-1.10), p=0.29 NS
Sensitivity analysis (excl. PSA >1.5) 4 650/4334 0.93 (0.80-1.08), p=0.35 NS
Metastasis-Free Survival
6m HT vs no HT 3 653/3364 0.82 (0.70-0.96), p=0.013 IMPROVED

Overall Survival

No clear improvement with HT overall
Similar effects for 6m and 24m duration
Results consistent in sensitivity analysis

Metastasis-Free Survival

6m HT significantly improves MFS
HR 0.82 (18% relative reduction)
24m HT data pending from 2 trials

Who Benefits from 24 Months ADT? (Individual Trial Data)

RTOG 9601 showed OS benefit with 24m ADT if:

  • Pre-salvage PSA >0.7 ng/mL
  • High Decipher genomic score (even at PSA 0.5-0.7)
  • No benefit if PSA ≤0.6 ng/mL

Consider risk stratification:

  • High-risk features may warrant 24m ADT
  • Meta-analysis masks subgroup effects
  • Individual patient data meta-analysis pending

⚠️ Critical Limitation: Node-Positive Disease

These results do NOT apply to pN1 patients! Most trials excluded node-positive disease. For pN1 patients, longer ADT duration (18-36 months) remains standard based on other evidence (e.g., RTOG 8531, EORTC 22961).

KEY MESSAGE: For pN0 disease - consider 24m ADT if PSA >0.7. For pN1 disease - longer ADT (18-36m) remains standard (not addressed in DADSPORT)

Key Takeaways: Salvage/Adjuvant Trials

  • Early salvage is now preferred over adjuvant RT
    • Similar oncologic outcomes
    • ~50% of patients avoid RT entirely
    • Lower toxicity (especially GU)
  • ADT benefit depends on pre-salvage PSA
    • RTOG 9601: Greatest benefit with PSA >0.7 ng/mL
    • Consider genomic classifiers (Decipher) for PSA 0.5-0.7
    • Limited benefit with PSA <0.5
  • Pelvic nodal RT considerations
    • SPPORT: Adding WPRT + ADT improved FFP
    • Consider in high-risk features (multiple risk factors)
  • Optimal salvage RT timing
    • Initiate at PSA 0.2-0.5 ng/mL
    • Modern trials used very low PSA thresholds

Part 2: Oligometastatic Prostate Cancer

  • Key Questions in Oligometastatic Disease:
    • Should we treat the primary tumor in M1 disease?
    • What is the role of metastasis-directed therapy?
    • How do we optimize systemic therapy?
    • What defines "oligometastatic" disease?
  • Trial Categories:
    • Treatment of primary in de novo M1
    • SBRT to oligometastases
    • Systemic therapy intensification

STAMPEDE Trial: Trial Arms

RT to Primary in M1 Disease

Eligibility: 2/3 of: T3/T4, PSA >40, GS 8-10 OR newly diagnosed N+/M1 | Arms: ADT + docetaxel ± RT (55 Gy/20 fx or 36 Gy/6 fx weekly)

Metastatic Burden Definitions

Low burden: <4 bone mets with none outside vertebra/pelvis AND no visceral mets

High burden: ≥4 bone mets with ≥1 outside vertebra/pelvis OR any visceral mets

Low Burden (Prespecified Analysis)

Overall Survival: IMPROVED (p=0.007)

  • 3-yr OS: 81% vs 73%
  • 5-yr OS: 65% vs 53%
  • Median OS: 85.5 vs 63.6 months
  • HR 0.68 (95% CI: 0.52-0.90)

Failure-Free Survival: IMPROVED (p<0.0001)

  • 3-yr FFS: 40% vs 23%

Exploratory: ≤3 Bone Mets

OS IMPROVED: 3-yr 85% vs 75%

FFS IMPROVED: 3-yr 53% vs 33%

High Burden: NO BENEFIT

  • 3-yr OS: 52-53% both arms (NS)
  • 5-yr OS: No difference (NS)
  • 3-yr FFS: 15-16% both arms (NS)

Additional Findings

RT Fractionation:

55 Gy/20 fx better FFS

vs

36 Gy weekly (no OS difference)

Toxicity: Grade 3-4 during RT: 5%, after RT: 4%

KEY MESSAGE: RT to prostate significantly improves OS in low-burden M1 disease (NNT = 8 for OS benefit at 3 years)

Systemic Therapy Intensification in mHSPC

  CHAARTED LATITUDE TITAN PEACE-1
Patients • mHSPC
• N = 790
• Any volume		 • High-risk mHSPC
• N = 1199
• ≥2 of: GS≥8, ≥3 bone lesions, visceral mets		 • mHSPC
• N = 1052
• Any volume
• Prior docetaxel allowed		 • mHSPC
• N = 1172
• 2x2 factorial
• ADT + docetaxel as SOC
Arms → ADT alone
→ ADT + docetaxel x6 		→ ADT + placebo
→ ADT + abiraterone + prednisone 		→ ADT + placebo
→ ADT + apalutamide 		→ ADT + docetaxel
→ ADT + docetaxel + abiraterone
± RT to primary
Overall Survival IMPROVED (p<0.001):
• Median: 44.0 vs 57.6 mo
• HR 0.61 (0.47-0.80)
High volume: 32.2 vs 51.2 mo
Low volume: NR vs 63.5 mo (NS)		 IMPROVED (p<0.0001):
• Median: 36.5 vs 51.8 mo
• HR 0.66 (0.56-0.78)
• 3-yr OS: 49% vs 66%		 IMPROVED (p=0.005):
• 24-mo OS: 74.8% vs 82.4%
• HR 0.67 (0.51-0.89)
• Benefit in all subgroups		 IMPROVED in high volume (p=0.017):
• High: 3.5 vs 5.1 yrs
• HR 0.72 (0.55-0.95)
• Low volume: NR (immature)
Progression-Free Survival IMPROVED (p<0.001):
• Median clinical PFS: 19.8 vs 33.0 mo
• HR 0.60 (0.52-0.70)		 IMPROVED (p<0.0001):
• Median rPFS: 16.8 vs 33.0 mo
• HR 0.47 (0.40-0.55)		 IMPROVED (p<0.001):
• Median rPFS: NR vs NR
• HR 0.48 (0.39-0.60)
• 24-mo rPFS: 68.2% vs 83.3%		 IMPROVED (p<0.0001):
• Median rPFS: 2.0 vs 4.5 yrs
• HR 0.50 (0.40-0.62)
• High: 1.6 vs 4.1 yrs
• Low: 2.7 vs NR
Key Toxicity • Grade 3-4 neutropenia: 12% vs 15%
• Febrile neutropenia: 6% vs 7%		 • Grade 3+ HTN: 10% vs 22%
• Grade 3+ hypokalemia: 3% vs 12%		 • Rash: 6% vs 28%
• Hypothyroidism: 1% vs 8%		 • Grade 3+ toxicity: 52% vs 63%
• HTN: 13% vs 22%

KEY MESSAGE: All trials show consistent OS benefit with systemic intensification.
Doublet therapy ADT  + novel hormonal standard for all metastatic prostate cancer,
Triplet therapy (ADT + docetaxel + novel hormonal)  for high-volume disease

PEACE-1:

2x2 Factorial Design

Metastatic Hormone-Sensitive Prostate Cancer
N = 1172
↓
Standard arm:
ADT + docetaxel
Standard +
abiraterone
Standard +
RT (74 Gy/37 fx)
Standard +
abiraterone + RT

Key Results:

  • Adding abiraterone to ADT + docetaxel:
    • Median PFS: 2.0 vs 4.5 years
    • High burden median OS: 3.5 vs 5.1 years
  • Low burden + RT analysis:
    • 3-yr PFS: 3.0 yrs (SOC) vs 4.4 (abi) vs 2.6 (RT) vs 7.5 (RT+abi)
    • RT + abi significantly better than abi alone (p=0.019)
    • Median OS: 6.9 yrs (no RT) vs 7.5 yrs (RT), p=0.81

ORIOLE

Phase II Randomized Trial
Recurrent hormone-sensitive PCa • 1-3 metastases • s/p primary treatment
No ADT x 6 months • Testosterone >50 ng/dL
N = 54
↓
Randomization 2:1
↓
SBRT to all metastases
n = 36
↓
PRIMARY ENDPOINT (6 months):
• Progression: 19% (p=0.003)

SECONDARY ENDPOINTS:
• Median PFS: Not reached vs 5.8 mo (HR 0.30, p=0.002)
• New PSMA lesions at 6 mo: 16% vs 63% (p=0.006)
• Total consolidation failure: 31%
• T cell clonal expansion: Significant (p=0.03)

PATTERN OF FAILURE:
• 7/11 failures: untreated PSMA+ lesions
• Only 1 in-field failure
Observation
n = 18
↓
PRIMARY ENDPOINT (6 months):
• Progression: 61%

SECONDARY ENDPOINTS:
• Median PFS: 5.8 months
• New PSMA lesions at 6 mo: 63%
• Total consolidation failure: 91%

NOTE:
• Higher baseline Gleason scores in observation arm (imbalance)

KEY FINDINGS: SBRT significantly reduced progression (primary endpoint met), prolonged PFS, and induced systemic immune response

STOMP

Phase II Randomized Trial (p<0.20 significant)
Recurrent PCa • ≤3 mets on choline PET • Testosterone >50 ng/dL
PSA doubling time <12 months
N = 62
↓
Randomization 1:1
↓
SBRT or Surgery to all metastases
n = 31
↓
PRIMARY ENDPOINT:
• ADT-free survival: 21 mo (p=0.11)
• 3-yr ADT-free survival: improved

SECONDARY ENDPOINTS:
• No symptomatic progression
• No local progression of treated lesions
• 11 patients had repeat SBRT
• QOL: Similar to observation

KEY FINDING:
• 8-month delay in ADT initiation
• Fewer metastases in treatment arm (imbalance)
Observation
n = 31
↓
PRIMARY ENDPOINT:
• ADT-free survival: 13 months

ADT TRIGGERS:
• Progression to >3 metastases
• Local progression of known mets
• Symptomatic progression

NOTE:
• More metastases at baseline vs treatment arm

KEY FINDING: MDT delayed ADT initiation by 8 months (phase II criteria: p<0.20 considered significant)

ORIOLE & STOMP Pooled Analysis

  • Combined analysis of 116 patients from ORIOLE and STOMP
  • Results:
    • Median PFS: 11.9 vs 5.9 months favoring SBRT
    • Median time to castrate resistance: 18.3 vs 17 months (NS)
    • Median OS: Not reached in either arm
  • Subgroup analysis:
    • Benefit consistent across subgroups
    • No difference by number of metastases (1 vs 2-3)
    • No difference by location (nodal vs bone)
  • Conclusion: SBRT to oligometastases doubles PFS compared to observation

Advanced Oligometastatic Trials

EXTEND ARTO SABR-COMET
Patients • Oligorecurrent PCa
• ≤5 metastases
• Hormone-sensitive
• N = 87		 • Castrate-resistant PCa
• ≤3 non-visceral mets
• Starting abiraterone
• N = 157		 • 1-5 mets, any histology
• Controlled primary
• 18% prostate cancer
• N = 99
Arms → Intermittent ADT alone
→ SBRT + intermittent ADT
(2 mo ADT pre-SBRT)		 → Abiraterone + prednisone
→ SBRT + abiraterone + prednisone 		→ Palliative SOC
→ SBRT + palliative SOC
(30-60 Gy/3-8 fx)
Overall Survival Not reported (ongoing) Not mature IMPROVED (p=0.006):
• Median: 28 vs 50 mo
• 5-yr: 18% vs 42%
• 8-yr: 14% vs 27%
Progression-Free Survival IMPROVED (HR 0.25, p<0.001):
• Median: 15.8 mo vs NR
• Improved T-cell activation 		IMPROVED (HR 0.35):
• Median time to progression improved 		IMPROVED (p=0.001):
• Median: 6.0 vs 12 mo
• 8-yr: 0% vs 21%
Key Secondary Endpoints Eugonad PFS IMPROVED:
• 6.1 mo vs NR
• Allows intermittent ADT 		6-mo biochemical response:
• ≥50% decline: 68% vs 92%
• PSA ≤0.2: 23% vs 56% 		• Local control: 46% vs 63%
• 11/25 long-term survivors had no progression
• 5/25 had salvage SBRT
Toxicity • Grade 3+: minimal
• No grade 4-5 events		 • Grade 3+: 6%
• Well tolerated		 • Grade 5: 4.5% (n=3) vs 0%
• Grade 3+: increased
• No deaths in other SBRT trials

KEY MESSAGES: SBRT improves PFS across settings. SABR-COMET showed OS benefit (phase II). EXTEND allows intermittent ADT. ARTO benefits even in CRPC.

Key Takeaways: Oligometastatic Disease

  • Treatment of primary in M1 disease:
    • Benefits low-volume disease (≤3 mets or CHAARTED low burden)
    • No benefit for high-volume or visceral metastases
    • Standard dose (55 Gy/20 fx) preferred over weekly hypofractionation
  • Metastasis-directed therapy:
    • Doubles PFS in oligorecurrent disease
    • Can delay ADT initiation by 8-12 months
    • May allow for intermittent ADT (EXTEND trial)
    • Benefits seen even in CRPC (ARTO trial)
  • Systemic therapy intensification:
    • Doublet therapy: ADT + novel hormonal agent or docetaxel now standard for mHSPC
    • Triplet therapy: (ADT + docetaxel + abiraterone) for high-volume disease
    • Consider RT to primary: (+ RT to primary) for low-volume disease
  • Future directions:
    • Optimal patient selection (PSMA PET, genomics)
    • Sequencing of local and systemic therapies
    • Role of immunotherapy combinations
    • Role of lutetium in early stage 

Summary

  • Salvage/Adjuvant RT:
    • Early salvage preferred over adjuvant (ARTISTIC meta-analysis)
    • Add ADT for PSA >0.7 (RTOG 9601)
    • Consider WPRT for high-risk features (SPPORT)
  • Oligometastatic Disease:
    • Treat primary for low-volume M1 (STAMPEDE)
    • SBRT to oligomets improves PFS and delays ADT
    • Systemic intensification improves OS in mHSPC
  • Clinical Integration:
    • PSMA PET changing detection of oligometastatic disease
    • Genomic classifiers help personalize treatment
    • Multidisciplinary approach essential